tbuckley/cabot-search huggingface dataset:
P29 The use of adjunct oral methotrexate as primary prevention for keloid scarring following syndactyly release surgery
Authors: Cathryn Sprenger, Andrew Fleming, Leila Ferguson, Alya Abdul-Wahab
Journal: British Journal of Dermatology (2023)

Abstract A 12-month-old Asian female underwent syndactyly release surgery with advancement flap closure of the first web space of the right hand. The procedure was complicated by enlarging keloids over the surgical site and dactylitis, a rare complication with only a few previously reported cases [Muzaffar AR, Rafols F, Masson J et al. Keloid formation after syndactyly reconstruction: associated conditions, prevalence, and preliminary report of a treatment method. J Hand Surg Am 2004; 29: 201–8. https://doi.org/10.1016/j.jhsa.2003.10.017]. Initial treatment of the keloid scarring with intralesional triamcinolone under general anaesthetic was unsuccessful. Subsequently, we elected to surgically excise the keloids closing with a full-thickness skin graft from the groin, with adjunct oral methotrexate (0.4 mg kg–1 weekly) for 9 months post-surgery. The use of oral methotrexate for this indication is rarely reported: one series included two cases of successful keloid suppression with 4 years of follow-up [Muzaffar et al.] and another series of four patients with successful keloid suppression after surgery for syndactyly with dactylitis [Tolerton SK, Tonkin MA. Keloid formation after syndactyly release in patients with associated macrodactyly: management with methotrexate therapy. J Hand Surg Eur 2011; 36: 490–7]. Low-dose methotrexate exerts anti-inflammatory effects by stimulating adenosine A2 receptors and increasing adenosine release at sites of inflammation, such as surgical sites [Muzaffar et al.]. In our patient, methotrexate was well-tolerated, keloid recurrence and dactylitis were avoided, and range of movement and functioning of the digits was maintained. Keloid formation after syndactyly release poses a complex management challenge and we propose methotrexate should be considered as an adjunct to reduce recurrence risk.
P20 Job syndrome: hyper IgE syndrome in a young girl with an acneiform rash
Authors: Tom Hefferon, Berbie Byrne, Marion Leahy, Annette Murphy
Journal: British Journal of Dermatology (2023)

Abstract Hyper IgE syndrome (HIES1) is a rare, autosomal dominant, primary immunodeficiency characterized by eczema, recurrent staphylococcal skin infections, pneumonia, increased serum IgE and eosinophilia. It is caused by a heterozygous mutation in the STAT3 gene on chromosome 17q21 with variable expressivity. Nonimmunological findings including characteristic facies, hyperextensibility, long-bone fractures, aneurysms, craniosynostosis and dental abnormalities. We present the case of an 11-year-old girl referred to dermatology with an acneiform facial rash. Examination was consistent with papulo-pustular scarring acne of the face and back. Her history was also significant for recurrent MSSA bacterial lymphadenitis requiring incision and drainage over the proceeding 3 years. Her past medical history was significant for the development of moderate-severity infantile acne at 2 weeks of age, mild childhood eczema, recurrent childhood otitis media Staphylococcus infections resulting in grommet insertion, primary tooth retention requiring extraction and a fractured wrist at age 9 years. Because of the burden of infection the patient was referred to immunology in Crumlin. Investigations revealed mild neutropenia, marginally elevated IgA and IgM, normal eosinophils, marginally elevated IgE, normal lymphocyte subsets, intact complement pathways and normal oxidative burst test. Next-generation sequencing was significant for STAT3 gene mutation consistent with HIES. As there is no family history this likely represents a de novo mutation. The patient is currently on prophylactic azithromycin and low-dose isotretinoin with good effect. This case represents a patient with both immunological and nonimmunological features of HIES1, marginally elevated IgE, absence of eosinophils and negative family history.
Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): a global, prospective, randomised controlled trial
Authors: Bruce L Wilkoff, Gerasimos Filippatos, Christophe Leclercq, Michael R Gold, Ahmad S Hersi, Kengo Kusano, Wilfried Mullens, G Michael Felker, Charan Kantipudi, Mikhael F El-Chami, Vidal Essebag, Bertrand Pierre, Francois Philippon, Francisco Perez-Gil, Eugene S Chung, Juan Sotomonte, Stanley Tung, Balbir Singh, Babak Bozorgnia, Satish Goel, Hans Holger Ebert, Niraj Varma, Kara J Quan, Fiorella Salerno, Bart Gerritse, Janelle van Wel, Daniel E Schaber, Dedra H Fagan, David Birnie
Journal: The Lancet (2023)
Hepatitis B and C in Europe: an update from the Global Burden of Disease Study 2019
Authors: Paolo Angelo Cortesi, Carla Fornari, Sara Conti, Ippazio Cosimo Antonazzo, Pietro Ferrara, Ayman Ahmed, Catalina Liliana Andrei, Tudorel Andrei, Anton A Artamonov, Maciej Banach, Carl Michael Baravelli, Till Winfried Bärnighausen, Akshaya Srikanth Bhagavathula, Nikolay Ivanovich Briko, Daniela Calina, Giulia Carreras, Sheng-Chia Chung, Mostafa Dianatinasab, Eleonora Dubljanin, Oyewole Christopher Durojaiye, Ifeanyi Jude Ezeonwumelu, Adeniyi Francis Fagbamigbe, Florian Fischer, Silvano Gallus, Ekaterina Vladimirovna Glushkova, Davide Golinelli, Giuseppe Gorini, Shoaib Hassan, Simon I Hay, Mihaela Hostiuc, Irena M Ilic, Milena D Ilic, Mihajlo Jakovljevic, Elham Jamshidi, Jacek Jerzy Jozwiak, Zubair Kabir, Joonas H Kauppila, Rovshan Khalilov, Moien AB Khan, Khaled Khatab, Ai Koyanagi, Carlo La Vecchia, Jeffrey V Lazarus, Caterina Ledda, Miriam Levi, Platon D Lopukhov, Joana A Loureiro, Philippa C Matthews, Alexios-Fotios A Mentis, Tomislav Mestrovic, Babak Moazen, Shafiu Mohammed, Lorenzo Monasta, Francesk Mulita, Christopher J L Murray, Ionut Negoi, Bogdan Oancea, Claudia Palladino, Jay Patel, Ionela-Roxana Petcu, Maarten J Postma, David Laith Rawaf, Salman Rawaf, Esperanza Romero-Rodríguez, Milena M Santric-Milicevic, Valentin Yurievich Skryabin, Anna Aleksandrovna Skryabina, Rafael Tabarés-Seisdedos, Mircea Tampa, Nuno Taveira, Arulmani Thiyagarajan, Marcos Roberto Tovani-Palone, Ronny Westerman, Mikhail Sergeevich Zastrozhin, Giampiero Mazzaglia, Lorenzo Giovanni Mantovani
Journal: The Lancet Public Health (2023)

In 2016, the World Health Assembly adopted the resolution to eliminate viral hepatitis by 2030. This study aims to provide an overview of the burdens of hepatitis B virus (HBV) and hepatitis C virus (HCV) in Europe and their changes from 2010 to 2019 using estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.
Advancing urban green and blue space contributions to public health
Authors: Ruth Fiona Hunter, Mark Nieuwenhuijsen, Carlo Fabian, Niamh Murphy, Kelly O'Hara, Erja Rappe, James Fleming Sallis, Estelle Victoria Lambert, Olga Lucia Sarmiento Duenas, Takemi Sugiyama, Sonja Kahlmeier
Journal: The Lancet Public Health (2023)
The path to Universal Health Coverage
Authors: None The Lancet Public Health
Journal: The Lancet Public Health (2023)

The UN High-Level Meeting on Universal Health Coverage (UHC) will take place on Sept 21, 2023, with the aim of providing countries and stakeholders with an opportunity to reinvigorate progress towards UHC—delivering "health for all" and creating resilient and equitable health systems in countries. Despite multiple pledges, together with the 2019 UN Political Declaration, too many countries have neither universal health coverage nor reliable long-term funding for health-system strengthening. Is UHC a destination or an aspiration to be constantly fought for?
Educational and social inequalities and cause-specific mortality in Mexico City: a prospective study
Authors: Thomas Addey, Jesus Alegre-Díaz, Fiona Bragg, Eirini Trichia, Rachel Wade, Rogelio Santacruz-Benitez, Raúl Ramirez-Reyes, Adrián Garcilazo-Ávila, Carlos Gonzáles-Carballo, Omar Yaxmehen Bello-Chavolla, Neftali Eduardo Antonio-Villa, Diego Aguilar-Ramirez, Louisa Gnatiuc Friedrichs, Sarah Lewington, Richard Peto, Rory Collins, Jaime Berumen, Jonathan R Emberson, Pablo Kuri-Morales, Roberto Tapia-Conyer
Journal: The Lancet Public Health (2023)

Social inequalities in adult mortality have been reported across diverse populations, but there is no large-scale prospective evidence from Mexico. We aimed to quantify social, including educational, inequalities in mortality among adults in Mexico City.
Potentially modifiable dementia risk factors in all Australians and within population groups: an analysis using cross-sectional survey data
Authors: Rhiann Sue See, Fintan Thompson, Sarah Russell, Rachel Quigley, Adrian Esterman, Linton R Harriss, Zoë Hyde, Sean Taylor, Kylie Radford, Dina LoGiudice, Robyn McDermott, Gill Livingston, Edward Strivens
Journal: The Lancet Public Health (2023)

Dementia is the second leading cause of disease burden in Australia. We aimed to calculate the population attributable fractions (PAFs) of dementia attributable to 11 of 12 previously identified potentially modifiable health and social risk factors (less education, hearing loss, hypertension, obesity, smoking, depression, social isolation, physical inactivity, diabetes, alcohol excess, air pollution, and traumatic brain injury), for Australians overall and three population groups (First Nations, and those of European and Asian ancestry).We calculated the prevalence of dementia risk factors (excluding traumatic brain injury) and PAFs, adjusted for communality, from the cross-sectional National Aboriginal and Torres Strait Islander Health Survey (2018-19), National Aboriginal and Torres Strait Islander Social Survey (2014-15), National Health Survey (2017-18), and General Social Survey (2014) conducted by the Australian Bureau of Statistics. We conducted sensitivity analyses using proxy estimates for traumatic brain injury (12th known risk factor) for which national data were not available.A large proportion (38·2%, 95% CI 37·2-39·2) of dementia in Australia was theoretically attributable to the 11 risk factors; 44·9% (43·1-46·7) for First Nations Australians, 36·4% (34·8-38·1) for European ancestry, and 33·6% (30·1-37·2) for Asian ancestry. Including traumatic brain injury increased the PAF to 40·6% (39·6-41·6) for all Australians. Physical inactivity (8·3%, 7·5-9·2), hearing loss (7·0%, 6·4-7·6), and obesity (6·6%, 6·0-7·3) accounted for approximately half of the total PAF estimates across Australia, and for all three population groups.Our PAF estimates indicate a substantial proportion of dementia in Australia is potentially preventable, which is broadly consistent with global trends and results from other countries. The highest potential for dementia prevention was among First Nations Australians, reflecting the enduring effect of upstream social, political, environmental, and economic disadvantage, leading to greater life-course exposure to dementia risk factors. Although there were common dementia risk factors across different population groups, prevention strategies should be informed by community consultation and be culturally and linguistically appropriate.Australian National Health and Medical Research Council and University College London Hospitals' National Institute for Health Research (NIHR) Biomedical Research Centre, and North Thames NIHR Applied Research Collaboration.
Identification of the natural chalcone glycoside hydroxysafflor yellow A as a suppressor of P53 overactivation‐associated hematopoietic defects
Authors: Jing Chen, Can Ren, Chong Yao, Mirko Baruscotti, Yi Wang, Lu Zhao
Journal: MedComm (2023)

Abstract Enhanced P53 signaling may lead to hematopoietic disorders, yet an effective therapeutic strategy is still lacking. Our study, along with previous research, suggests that P53 overactivation and hematopoietic defects are major consequences of zinc deficiency. However, the relationship between these two pathological processes remains unclear. In this study, we observed a severe reduction in the number of hematopoietic stem cells (HSCs) and multi‐lineage progenitor cells in zebrafish treated with the zinc chelator N , N , N ′, N ′‐tetrakis(2‐pyridylmethyl)ethylenediamine and showed the indispensable role of P53 signaling in the process. Next, we took advantage of HSCs‐labeled transgenic zebrafish and conducted a highly efficient phenotypic screening for small molecules against P53‐dependent hematopoietic disorders. Hydroxysafflor yellow A (HSYA), a natural chalcone glycoside, exhibited potent protection against hematopoietic failure in zinc‐deficient zebrafish and strongly inhibited the P53 pathway. We confirmed the protective effect of HSYA in zinc‐deficient mice bone marrow nucleated cells, which showed a significant suppression of P53 signaling and oxidative stress. Furthermore, the hematopoietic‐protective activity of HSYA was validated using a mice model of myelotoxicity induced by 5‐FU. In summary, our work provides an effective phenotypic screening strategy for identifying hematopoietic‐protective agents and reveals the novel role of HSYA as a promising lead compound in rescuing hematopoietic disorders associated with P53 overactivation.
Targeting drug‐tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells
Authors: Xiaohai Song, Yang Lan, Xiuli Zheng, Qianyu Zhu, Xuliang Liao, Kai Liu, Weihan Zhang, QiangBo Peng, Yunfeng Zhu, Linyong Zhao, Xiaolong Chen, Yang Shu, Kun Yang, Jiankun Hu
Journal: MedComm (2023)

Drug resistance remains the greatest challenge in improving outcomes for cancer patients who receive chemotherapy and targeted therapy. Surmounting evidence suggests that a subpopulation of cancer cells could escape intense selective drug treatment by entering a drug-tolerant state without genetic variations. These drug-tolerant cells (DTCs) are characterized with a slow proliferation rate and a reversible phenotype. They reside in the tumor region and may serve as a reservoir for resistant phenotypes. The survival of DTCs is regulated by epigenetic modifications, transcriptional regulation, mRNA translation remodeling, metabolic changes, antiapoptosis, interactions with the tumor microenvironment, and activation of signaling pathways. Thus, targeting the regulators of DTCs opens a new avenue for the treatment of therapy-resistant tumors. In this review, we first provide an overview of common characteristics of DTCs and the regulating networks in DTCs development. We also discuss the potential therapeutic opportunities to target DTCs. Last, we discuss the current challenges and prospects of the DTC-targeting approach to overcome acquired drug resistance. Reviewing the latest developments in DTC research could be essential in discovering of methods to eliminate DTCs, which may represent a novel therapeutic strategy for preventing drug resistance in the future.
Infiltrating CD8+ T cells exacerbate Alzheimer’s disease pathology in a 3D human neuroimmune axis model
Authors: Mehdi Jorfi, Joseph Park, Clare K. Hall, Chih-Chung Jerry Lin, Meng Chen, Djuna von Maydell, Jane M. Kruskop, Byunghoon Kang, Younjung Choi, Dmitry Prokopenko, Daniel Irimia, Doo Yeon Kim, Rudolph E. Tanzi
Journal: Nature Neuroscience (2023)
Inhibition of tumor intrinsic BANF1 activates antitumor immune responses via cGAS-STING and enhances the efficacy of PD-1 blockade
Authors: Minglei Wang, Yiheng Huang, Minxin Chen, Weiyan Wang, Fei Wu, Tao Zhong, Xiaozheng Chen, Fei Wang, Yang Li, Jinming Yu, Meng Wu, Dawei Chen
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background BANF1 is well known as a natural opponent of cyclic GMP-AMP synthase (cGAS) activity on genomic self-DNA. However, the roles of BANF1 in tumor immunity remain unclear. Here, we investigate the possible impact of BANF1 on antitumor immunity and response to immunotherapy. Methods The Cancer Genome Atlas public data were analyzed to evaluate the relevance of the expression of BANF1, patients’ survival and immune cell infiltration. We monitored tumor growth and explored the antitumor efficacy of targeting tumor-intrinsic BANF1 in combination with anti-programmed cell death protein-1 (PD-1) in MC38 or B16F10 tumor models in both immunocompetent and immunodeficient mice. Flow cytometry, immunofluorescence and T cells depletion experiments were used to validate the role of BANF1 in tumor immune microenvironment reprogramming. RNA sequencing was then used to interrogate the mechanisms how BANF1 regulated antitumor immunity. Results We show that upregulated expression of BANF1 in tumor tissues is significantly associated with poor survival and is negatively correlated with immune cell infiltration. Deficiency of BANF1 in tumor cells markedly antagonizes tumor growth in immunocompetent but not immunocompromised mice, and enhances the response to immunotherapy in murine models of melanoma and colon cancer. In the immunotherapy clinical cohort, patients with high BANF1 expression had a worse prognosis. Mechanistically, BANF1 knockout activates antitumor immune responses mediated by cGAS-synthase-stimulator of interferon genes (cGAS-STING) pathway, resulting in an immune-activating tumor microenvironment including increased CD8 + T cell infiltration and decreased myeloid-derived suppressor cell enrichment. Conclusions BANF1 is a key regulator of antitumor immunity mediated by cGAS-STING pathway. Therefore, our study provides a rational that targeting BANF1 is a potent strategy for enhancing immunotherapy for cancer with BANF1 upregulation.
Updating <i>Good Medical Practice</i> guidelines: a first step towards tackling sexism and sexual misconduct in healthcare
Authors: Chelcie Jewitt, Becky Cox
Journal: BMJ (2023)

Updating the General Medical Council’s <i>Good Medical Practice</i> guidelines is a positive step towards confronting sexism and sexual misconduct in healthcare, but reporting and support for survivors and witnesses must improve, write <b>Chelcie Jewitt</b> and <b>Becky Cox</b>
Nivolumab plus ipilimumab in advanced salivary gland cancer: a phase 2 trial
Authors: Joris L. Vos, Bharat Burman, Swati Jain, Conall W. R. Fitzgerald, Eric J. Sherman, Lara A. Dunn, James V. Fetten, Loren S. Michel, Anuja Kriplani, Kenneth K. Ng, Juliana Eng, Vatche Tchekmedyian, Sofia Haque, Nora Katabi, Fengshen Kuo, Catherine Y. Han, Zaineb Nadeem, Wei Yang, Vladimir Makarov, Raghvendra M. Srivastava, Irina Ostrovnaya, Manu Prasad, Charlotte L. Zuur, Nadeem Riaz, David G. Pfister, Christopher A. Klebanoff, Timothy A. Chan, Alan L. Ho, Luc G. T. Morris
Journal: Nature Medicine (2023)
Comprehensive analyses of partially methylated domains and differentially methylated regions in esophageal cancer reveal both cell-type- and cancer-specific epigenetic regulation
Authors: Yueyuan Zheng, Benjamin Ziman, Allen S. Ho, Uttam K. Sinha, Li-Yan Xu, En-Min Li, H Phillip Koeffler, Benjamin P. Berman, De-Chen Lin
Journal: Genome biology (2023)

Abstract Background As one of the most common malignancies, esophageal cancer has two subtypes, squamous cell carcinoma and adenocarcinoma, arising from distinct cells-of-origin. Distinguishing cell-type-specific molecular features from cancer-specific characteristics is challenging. Results We analyze whole-genome bisulfite sequencing data on 45 esophageal tumor and nonmalignant samples from both subtypes. We develop a novel sequence-aware method to identify large partially methylated domains (PMDs), revealing profound heterogeneity at both methylation level and genomic distribution of PMDs across tumor samples. We identify subtype-specific PMDs that are associated with repressive transcription, chromatin B compartments and high somatic mutation rate. While genomic locations of these PMDs are pre-established in normal cells, the degree of loss is significantly higher in tumors. We find that cell-type-specific deposition of H3K36me2 may underlie genomic distribution of PMDs. At a smaller genomic scale, both cell-type- and cancer-specific differentially methylated regions (DMRs) are identified for each subtype. Using binding motif analysis within these DMRs, we show that a cell-type-specific transcription factor HNF4A maintains the binding sites that it generates in normal cells, while establishing new binding sites cooperatively with novel partners such as FOSL1 in esophageal adenocarcinoma. Finally, leveraging pan-tissue single-cell and pan-cancer epigenomic datasets, we demonstrate that a substantial fraction of cell-type-specific PMDs and DMRs identified here in esophageal cancer are actually markers that co-occur in other cancers originating from related cell types. Conclusions These findings advance our understanding of DNA methylation dynamics at various genomic scales in normal and malignant states, providing novel mechanistic insights into cell-type- and cancer-specific epigenetic regulations.
Tailored psychological intervention for anxiety or depression in COPD (TANDEM): a randomised controlled trial
Authors: Stephanie J.C. Taylor, Ratna Sohanpal, Liz Steed, Karen Marshall, Claire Chan, Nahel Yaziji, Amy C. Barradell, Paulino Font-Gilabert, Andrew Healey, Richard Hooper, Moira J. Kelly, Kristie-Marie Mammoliti, Stefan Priebe, Arvind Rajasekaran, C. Michael Roberts, Vickie Rowland, Sally J. Singh, Melanie Smuk, Martin Underwood, Sarah Waseem, Patrick White, Vari Wileman, Hilary Pinnock
Journal: European Respiratory Journal (2023)

Background The TANDEM multicentre, pragmatic, randomised controlled trial evaluated whether a tailored psychological intervention based on a cognitive behavioural approach for people with COPD and symptoms of anxiety and/or depression improved anxiety or depression compared with usual care (control). Methods People with COPD and moderate to very severe airways obstruction and Hospital Anxiety and Depression Scale subscale scores indicating mild to moderate anxiety (HADS-A) and/or depression (HADS-D) were randomised 1.25:1 (242 intervention and 181 control). Respiratory health professionals delivered the intervention face-to-face over 6–8 weeks. Co-primary outcomes were HADS-A and HADS-D measured 6 months post-randomisation. Secondary outcomes at 6 and 12 months included: HADS-A and HADS-D (12 months), Beck Depression Inventory II, Beck Anxiety Inventory, St George's Respiratory Questionnaire, social engagement, the EuroQol instrument five-level version (EQ-5D-5L), smoking status, completion of pulmonary rehabilitation, and health and social care resource use. Results The intervention did not improve anxiety (HADS-A mean difference −0.60, 95% CI −1.40–0.21) or depression (HADS-D mean difference −0.66, 95% CI −1.39–0.07) at 6 months. The intervention did not improve any secondary outcomes at either time-point, nor did it influence completion of pulmonary rehabilitation or healthcare resource use. Deaths in the intervention arm (13/242; 5%) exceeded those in the control arm (3/181; 2%), but none were associated with the intervention. Health economic analysis found the intervention highly unlikely to be cost-effective. Conclusion This trial has shown, beyond reasonable doubt, that this cognitive behavioural intervention delivered by trained and supervised respiratory health professionals does not improve psychological comorbidity in people with advanced COPD and depression or anxiety.